Ezra Cohen, MD: We’ve heard a lot now about immunotherapy and where it stands in head and neck cancer. I want to turn to each one of our panelists and get their take on where immunotherapy stands right now for patients with head and neck cancer. Barbara?

Barbara A. Burtness, MD: I think it’s a new day. For many years, we’ve put many patients on clinical trials that have not yielded any changes in therapy, and now we see that there are agents, which, albeit it not with a very high response rate, can lead to durable responses and improved survival in patients with platinum refractory disease, and that’s a wonderful thing.

Jared Weiss, MD: These agents are absolutely inspiring, but they also do have real risks and toxicities, and those risks and toxicities are different than the profile that we’re used to seeing with cytotoxic therapies. And so, I think it’s important to learn about those specific toxicities, such as hypothyroidism, that we see at particularly high rates in head and neck cancer, and learn to respond to them quickly. To not hold off, not try to maximize benefit, to have early initiation of steroids and early consultation, either with an oncologist with more experience in treating these agents or with other specialties, where appropriate, at a low threshold.

Ezra Cohen, MD: I think it’s a great point that we have to keep in mind that these are agents with different mechanisms of actions and therefore different toxicities. In a sense, the oncology community has turned to the rheumatology community to deal with all the inflammatory reactions, or some of the inflammatory reactions, to immunotherapy. So, thanks, Jared. That’s a great point. Josh, what’s your take on immunotherapy where it stands now?

Joshua M. Bauml, MD: I think that, as Barbara and Jared said, it’s very, very exciting. These are exciting drugs with significant activity, but we should not let our fervor for this excitement lead us astray. Specifically, there’s this concept of pseudoprogression that we think about with immunotherapy, where the T cells rush into the tumor—and it’s a very nice story—and it swells, and it gets bigger. But the problem is that the majority of the time, when a patient has a tumor that’s growing, especially in head and neck cancer, they’re probably having progressive disease. We need to withhold that excitement and really look at the patient in front of us and say, “If they’re symptomatic and their tumor is getting bigger, we’ve got to look elsewhere.” We’ve got to consider clinical trials. We’ve got to consider another approach to treat that patient.

Ezra Cohen, MD: Great points. So, now that immunotherapy is established in head and neck cancer, at least in the form of anti-PD-1, let’s look to the future. We now have seen some data about promising trials with immunotherapy. What do you expect, Josh, in the rest of 2017 and 2018?

Joshua M. Bauml, MD: Well, I think that, really, the key next step is how we can expand that degree of response rate. Right now, we’ve got an exciting but limited response rate. So, is that increasing response something we can achieve through combination therapies? We can combine the immunotherapies that we know—things like nivolumab and pembrolizumab—but also PD-L1 inhibitors and other immunotherapeutics with chemotherapy, with radiation, and with other immunotherapeutics utilizing other checkpoint inhibitors. I think it’s really a new day of evaluating how to do those combinations in a rational fashion, and I think that’s a critical point.

Transcript Edited for Clarity

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Transcript:

Ezra Cohen, MD: We’ve heard a lot now about immunotherapy and where it stands in head and neck cancer. I want to turn to each one of our panelists and get their take on where immunotherapy stands right now for patients with head and neck cancer. Barbara?

Barbara A. Burtness, MD: I think it’s a new day. For many years, we’ve put many patients on clinical trials that have not yielded any changes in therapy, and now we see that there are agents, which, albeit it not with a very high response rate, can lead to durable responses and improved survival in patients with platinum refractory disease, and that’s a wonderful thing.

Jared Weiss, MD: These agents are absolutely inspiring, but they also do have real risks and toxicities, and those risks and toxicities are different than the profile that we’re used to seeing with cytotoxic therapies. And so, I think it’s important to learn about those specific toxicities, such as hypothyroidism, that we see at particularly high rates in head and neck cancer, and learn to respond to them quickly. To not hold off, not try to maximize benefit, to have early initiation of steroids and early consultation, either with an oncologist with more experience in treating these agents or with other specialties, where appropriate, at a low threshold.

Ezra Cohen, MD: I think it’s a great point that we have to keep in mind that these are agents with different mechanisms of actions and therefore different toxicities. In a sense, the oncology community has turned to the rheumatology community to deal with all the inflammatory reactions, or some of the inflammatory reactions, to immunotherapy. So, thanks, Jared. That’s a great point. Josh, what’s your take on immunotherapy where it stands now?

Joshua M. Bauml, MD: I think that, as Barbara and Jared said, it’s very, very exciting. These are exciting drugs with significant activity, but we should not let our fervor for this excitement lead us astray. Specifically, there’s this concept of pseudoprogression that we think about with immunotherapy, where the T cells rush into the tumor—and it’s a very nice story—and it swells, and it gets bigger. But the problem is that the majority of the time, when a patient has a tumor that’s growing, especially in head and neck cancer, they’re probably having progressive disease. We need to withhold that excitement and really look at the patient in front of us and say, “If they’re symptomatic and their tumor is getting bigger, we’ve got to look elsewhere.” We’ve got to consider clinical trials. We’ve got to consider another approach to treat that patient.

Ezra Cohen, MD: Great points. So, now that immunotherapy is established in head and neck cancer, at least in the form of anti-PD-1, let’s look to the future. We now have seen some data about promising trials with immunotherapy. What do you expect, Josh, in the rest of 2017 and 2018?

Joshua M. Bauml, MD: Well, I think that, really, the key next step is how we can expand that degree of response rate. Right now, we’ve got an exciting but limited response rate. So, is that increasing response something we can achieve through combination therapies? We can combine the immunotherapies that we know—things like nivolumab and pembrolizumab—but also PD-L1 inhibitors and other immunotherapeutics with chemotherapy, with radiation, and with other immunotherapeutics utilizing other checkpoint inhibitors. I think it’s really a new day of evaluating how to do those combinations in a rational fashion, and I think that’s a critical point.